Biochem - Metabolism (Part 2) Flashcards
1
Q
Where in the cell is the enzyme glucose-6-phosphatase found?
A
Endoplasmic reticulum
2
Q
In which tissues are the enzymes of gluconeogenesis found?
A
Liver, kidney, and intestinal epithelium
3
Q
What product of the pentose phosphate pathway (hexose monophosphate shunt) facilitates steroid and fatty acid synthesis?
A
NADPH
4
Q
What is the function of NADPH in the erythrocyte?
A
It reduces glutathione
5
Q
What are the two phases of the hexose monophosphate shunt (pentose phosphate pathway)?
A
Irreversible oxidative phase and reversible nonoxidative phase
6
Q
What key enzyme regulates the oxidative phase of the hexose monophosphate shunt?
A
Glucose-6-phosphate dehydrogenase
7
Q
How many adenosine triphosphate molecules are used and produced by the hexose monophosphate shunt (pentose phosphate pathway)?
A
Zero
8
Q
What vitamin is required for the nonoxidative phase of the hexose monophosphate shunt?
A
The transketolases that catalyze the nonoxidative reactions require thiamine (vitamin B1) as a cofactor
9
Q
What four products are formed after both phases of the hexose monophosphate shunt?
A
Ribose-5-phosphate, G3P, F6P, and NADPH are the products
10
Q
Which product of the hexose monophosphate shunt is used in nucleotide synthesis?
A
Ribose-5-phosphate
11
Q
How are G3P and F6P utilized in the cell following the hexose monophosphate shunt?
A
These are glycolytic intermediates and can enter glycolysis
12
Q
Name three sites of fatty acid or steroid synthesis that show high pentose phosphate pathway (hexose monophosphate shunt) activity.
A
Lactating mammary glands, liver, adrenal cortex
13
Q
Do the reactions of the hexose monophosphate shunt (pentose phosphate pathway) take place in the mitochondria or the cytosol of a cell?
A
The cytosol
14
Q
Where would you find elevated activity of the pentose phosphate pathway, but no fatty acid or steroid synthesis?
A
In the red blood cells; the reducing equivalents formed are necessary to neutralize oxidative radicals
15
Q
Name two cells that utilize NADPH for an oxidative burst.
A
Neutrophils, macrophages
16
Q
During the oxygen-dependent respiratory burst used by neutrophils to destroy bacteria, what enzyme converts hydrogen peroxide to bleach (hypochlorite) in the presence of chloride ion?
A
Myeloperoxidase, which is found in neutrophil azurophilic granules
17
Q
Why would you expect cells like neutrophils and macrophages to have high concentrations of NADPH oxidase?
A
It is important for the immune response, rapidly releasing reactive oxygen species to kill bacteria
18
Q
What disease is caused by a deficiency of NADPH oxidase?
A
Chronic granulomatous disease; a genetic immunodeficiency
19
Q
During the oxygen-dependent respiratory burst that is used by neutrophils to destroy bacteria, what enzyme converts oxygen to superoxide?
A
NADPH oxidase
20
Q
Which form of glutathione must be readily available in the cell to remove reactive oxygen species to prevent cell lysis?
A
The reduced form (GSH); reducing equivalents are created in the hexose monophosphate shunt
21
Q
Is glutathione reduced or oxidized when converting hydrogen peroxide to water in neutrophils?
A
Oxidized
22
Q
Regarding the neutrophil oxygen-dependent respiratory burst, which electron carrier is used to reduce glutathione after the conversion of hydrogen peroxide to water?
A
NADPH
23
Q
During the oxygen-dependent respiratory burst that is used by neutrophils to destroy bacteria, what enzyme converts superoxide to hydrogen peroxide?
A
Superoxide dismutase
24
Q
During the oxygen-dependent respiratory burst that is used by neutrophils to destroy bacteria, what enzyme converts hydrogen peroxide to water in the presence of glutathione?
A
Catalase
25
What enzyme uses NADPH to replenish reduced glutathione?
Glutathione reductase
26
What enzyme replenishes the NADPH used to reduce glutathione?
Glucose-6-phosphate dehydrogenase
27
What is the end product of the oxygen-dependent respiratory burst that is used to kill bacteria in the phagolysosome?
Bleach (HOCl, hypochlorite)
28
True or False? The white blood cells of patients with chronic granulomatous disease can utilize hydrogen peroxide generated by invading organisms and convert it to reactive oxygen intermediates.
TRUE
29
Patients with chronic granulomatous disease are at an increased risk for infection by which microorganisms?
Catalase-positive species like *Staphylococcus aureus* and *Aspergillus*
30
What substance detoxifies free radicals and peroxides in the cell?
Glutathione
31
What molecule is required to maintain a store of reduced glutathione?
NADPH
32
What enzyme is required to produce and maintain NADPH within the cell?
Glucose-6-phosphate dehydrogenase
33
What might you find on the peripheral smear of someone with glucose-6-phosphate dehydrogenase deficiency after they consume fava beans?
Hemolytic anemia (hence the reference to this condition as favism)
34
What property of fava beans, sulfonamides, primaquine, and antituberculosis drugs allows them to cause hemolytic anemia in persons with glucose-6-phosphate dehydrogenase deficiency?
They are all oxidizing agents, and cause oxidative stress to the erythrocyte
35
What are the precipitates of hemoglobin that are found on microscopy in the red blood cells of patients with glucose-6-phosphate dehydrogenase deficiency called?
Heinz bodies (remember: **H**einz bodies = precipitated **H**emoglobin)
36
Members of which populations are more likely to have glucose-6-phosphate dehydrogenase deficiency?
Mediterranean and African individuals
37
What is the most common human enzyme deficiency?
Glucose-6-phosphate dehydrogenase deficiency
38
Glucose-6-phosphate dehydrogenase deficiency shows what form of inheritance?
X-linked recessive; therefore, symptoms are largely seen in males
39
People with glucose-6-phosphate dehydrogenase deficiency have _____ (increased/decreased) malarial resistance.
increased; this likely accounts for the prevalence of the deficiency in African populations
40
Phagocytic removal of Heinz bodies from macrophages in patients with glucose-6-phosphate dehydrogenase deficiency results a specific appearance of red blood cells when viewed under a microscope termed ____ \_\_\_\_\_.
Bite cells
41
What disease is caused by a deficiency of aldolase B?
Fructose intolerance
42
What disease is caused by a defect in fructokinase?
Essential fructosuria
43
What type of disease inheritance is demonstrated in families with fructose intolerance?
Autosomal recessive
44
Patients with fructose intolerance accumulate what metabolic intermediate?
Fructose-1-phosphate
45
Which disorder of fructose metabolism involves the symptoms of hypoglycemia, jaundice, cirrhosis, and vomiting?
Fructose intolerance
46
Which causes milder symptoms: disorders of fructose metabolism or analogous disorders of galactose metabolism.
Disorders of fructose metabolism
47
Why does consumption of sucrose worsen the symptoms of fructose intolerance?
Sucrose is made of fructose and glucose
48
What is the mode of inheritance of fructose intolerance?
Autosomal recessive, as is the case with most enzyme deficiencies
49
What is the treatment for fructose intolerance?
Decreased fructose and sucrose intake
50
In fructose metabolism, the conversion of fructose into fructose-1-phosphate is catalyzed by what enzyme?
Fructokinase
51
Are patients with a deficiency of aldolase B (fructose intolerance) more likely to be hyperglycemic or hypoglycemic?
Hypoglycemic
52
In fructose metabolism, the conversion of fructose-1-phosphate into dihydroxyacetone phosphate plus glyceraldehyde is catalyzed by what enzyme?
Aldolase B; the resulting molecules can enter glycolysis
53
Which disorder of fructose metabolism causes more serious clinical sequelae?
Fructose intolerance
54
What molecule becomes scarce in fructose intolerance, resulting in inhibition of glycogenolysis and gluconeogenesis?
Phosphate
55
Galactosemia is caused by an absence of what enzyme?
Galactose-1-phosphate uridyltransferase
56
Which has milder symptoms: classic galactosemia, or galactokinase deficiency?
Galactokinase deficiency
57
What is the inheritance pattern of galactokinase deficiency?
Autosomal recessive
58
What enzyme interconverts UDP-glucose and UDP-galactose?
4-Epimerase
59
Galactitol is formed from galactose using which enzyme?
Aldose reductase
60
In galactose metabolism, the conversion of galactose-1-phosphate to glucose-1-phosphate is catalyzed by which enzyme?
Galactose-1-phosphate uridyltransferase; deficiency causes classic galactosemia
61
In galactose metabolism, a block in the conversion of galactose to galactose-1-phosphate is caused by what disease?
Galactokinase deficiency
62
In galactosemia, the build-up of which substance causes damage to organs?
Galactitol
63
What is the treatment for galactosemia?
Removing galactose and lactose from the diet
64
Cataracts, hepatosplenomegaly, and mental retardation are symptoms of what disorder of galactose metabolism?
Galactosemia; it is more severe than galactokinase deficiency
65
In galactose metabolism, a block in the conversion of galactose-1-phosphate to glucose-1-phosphate is caused by what disease?
Galactosemia
66
Galactosemia demonstrates what type of inheritance pattern?
Autosomal recessive
67
Glucose is converted to its alcohol counterpart, sorbitol, and thus trapped in the cell via what enzyme?
Aldose reductase
68
Some tissues convert sorbitol to fructose via what enzyme?
Sorbitol dehydrogenase
69
List the organs that have both aldose reductase and sorbitol dehydrogenase.
Liver, ovaries, and seminal vesicles
70
The enzymes aldose reductase and sorbitol dehydrogenase both require what cofactor?
NADPH
71
What organ has only aldose reductase and no sorbitol dehydrogenase?
Kidney
72
What type of cell in the nervous system has only aldose reductase and no sorbitol dehydrogenase?
Schwann cells
73
What parts of the eye have only aldose reductase and no sorbitol dehydrogenase?
Lens and retina
74
Why is sorbitol considered osmotically active?
Because of its inability to freely cross the membrane like glucose
75
In what disease is sorbitol accumulation common?
Diabetes
76
What three conditions are seen in chronic diabetes due to the osmotic damage caused by sorbitol?
Cataracts, retinopathy, peripheral neuropathy
77
What two sugars that are also converted to their respective alcohol forms via aldose reductase are considered osmotically active?
glucose and galactose
78
Which populations tend to be lactase deficient in adulthood?
Asian and African-American populations
79
A woman gets bloating, cramps, and diarrhea after eating milk and ice cream. What enzyme is likely deficient in this patient?
Lactase
80
What is the treatment for lactase deficiency?
Lactase pills or dietary avoidance of lactose
81
Lactase deficiency causes what type of diarrhea when lactose is consumed?
Osmotic diarrhea due to undigested sugars that are not absorbed in the small intestine
82
The amino acids found in proteins in the human body are ______ (R-form/L-form).
L-form
83
Name the four amino acids that are both glucogenic and ketogenic.
Isoleucine, phenylalanine, threonine, and tryptophan
84
Name the two purely ketogenic amino acids.
Leucine and lysine
85
Name the four amino acids that are purely glucogenic.
Methionine, valine, arginine, and histidine
86
Which two amino acids become essential during periods of rapid growth?
Arginine and histidine
87
What type of amino acids make up histones? Why?
Basic amino acids; the positive charge interacts with the negatively charged DNA to bind it in coils
88
What is the significance of an amino acid being considered essential?
It must come from the diet
89
Name the two acidic amino acids.
Aspartate and glutamate
90
Through what process can glucogenic amino acids be converted to glucose?
Gluconeogenesis
91
Name the amino acids that are basic.
Arginine, lysine and histidine
92
Which two amino acids are positively charged at body pH? Which are negatively charged?
Positive: arginine and lysine; Negative: aspartate and glutamate
93
The urea cycle ultimately yields \_\_\_\_\_\_, which is excreted in the urine, and \_\_\_\_\_, which can enter the citric acid cycle.
Urea; fumarate
94
In what organ does the urea cycle occur?
The liver
95
Does the urea cycle occur in the mitochondria, in the cytosol, or both?
Both
96
In the urea cycle, the formation of what substance occurs in the mitochondria (whereas the remaining steps occur in the cytosol)?
Carbamoyl phosphate
97
What amino acid is the immediate precursor to urea in the urea cycle?
Arginine
98
The urea cycle excretes an excess of which element generated by amino acid catabolism?
Nitrogen
99
What amino acid combines with citrulline to form arginosuccinate in the urea cycle?
Aspartate
100
What is the rate-limiting enzyme of the urea cycle?
Carbamoyl phosphate synthetase I
101
What reaction is catalyzed by carbamoyl phosphate synthetase I?
The conversion of CO2 and NH4 into carbamoyl phosphate, a process requiring 2 adenosine triphosphate
102
Where in the cell does the rate-limiting step of the urea cycle occur?
In the mitochondria
103
From which molecules are the nitrogen atoms in urea derived?
Ammonium and aspartate
104
What enzyme catalyzes the conversion of carbamoyl phosphate and ornithine into citrulline?
Ornithine transcarbamoylase
105
What are two metabolic fuels produced by amino acid catabolism?
Pyruvate and acetyl-CoA
106
What precursors are converted by arginosuccinate synthetase into arginosuccinate?
Citrulline and aspartate
107
What byproduct of the urea cycle is released by arginosuccinase?
Fumarate, which may enter the tricarboxylic acid cycle, whereas arginine is converted into urea and ornithine in the urea cycle
108
What is the enzyme that creates urea from arginine in the urea cycle?
Arginase
109
Ammonia is transported by which amino acid from the muscle to the liver to participate in urea formation?
Alanine
110
Trace the pathway of an ammonium group from its creation by amino acid catabolism in muscle to excretion.
It is donated to pyruvate to form alanine, which travels to the liver via blood, where it is donated to -ketoglutarate to form glutamate, which can be excreted via the urea cycle
111
Ammonia groups are transported from muscle to liver via which molecule?
Alanine
112
What is the fate of alanine in the liver after it donates its ammonia group to the urea cycle?
It becomes pyruvate and goes through gluconeogenesis
113
The addition of an ammonia group to -ketoglutarate produces what substance?
Glutamate
114
The addition of an ammonia group to pyruvate produces what substance?
Alanine
115
Name two categories of hyperammonemia and examples of each.
Acquired, as in liver failure; hereditary, as in urea cycle enzyme deficiencies
116
Excess ammonium depletes \_\_\_\_\_, leading to inhibition of the citric acid cycle.
-Ketoglutarate
117
Describe the clinical presentation of hyperammonemia.
Tremor, slurring of speech, somnolence, vomiting, cerebral edema, and blurring of vision
118
A patient presents with tremor, slurring of speech, somnolence, vomiting, cerebral edema, and blurring of vision, and is diagnosed with hyperammonemia. What two treatments could lower her serum ammonia levels?
Benzoate or phenylbutyrate
119
What is the most common urea cycle enzyme deficiency?
Ornithine transcarbamoylase deficiency
120
What is the inheritance pattern of ornithine transcarbamoylase deficiency?
X-linked recessive
121
You see a patient with a urea cycle enzyme deficiency, but have ruled out ornithine transcarbamoylase deficiency. What is the inheritance pattern?
Autosomal recessive (all urea cycle enzyme deficiencies except ornithine transcarbamoylase deficiency have this inheritance pattern)
122
How does ornithine transcarbamoylase deficiency present clinically?
Tremor, lethargy, vomiting in a neonate who may be found to have cerebral edema and elevated ammonia on lab studies
123
When would you most likely detect an ornithine transcarbamoylase deficiency in a patient?
Typically this is evident in the first days of life, but it may have later onset
124
What molecule is excess carbamoyl phosphate converted into?
Orotic acid
125
What serum finding is diagnostic of ornithine transcarbamoylase deficiency?
Elevated orotic acid
126
A newborn patient has a blood test which shows increased orotic acid, low BUN, and increased ammonia; what disease do you suspect?
Ornithine transcarbamoylase deficiency
127
Which amino acid is the parent compound of tyrosine, thyroxine, dopa, melanin, dopamine, norepinephrine, and epinephrine?
Phenylalanine
128
What amino acid is the parent compound of niacin, serotonin, and melatonin?
Tryptophan
129
From which amino acid is histamine derived?
Histidine
130
From which amino acid is heme derived?
Glycine
131
Which amino acid is the parent compound of creatine, urea, and nitric oxide?
Arginine
132
From which amino acid is γ-aminobutyric acid derived?
Glutamate
133
From which amino acid is porphyrin derived?
Glycine
134
From which amino acid are NAD+ and NADP+ derived?
Tryptophan
135
The reaction in which GABA is derived from glutamate is catalyzed by which enzyme?
Glutamate decarboxylase; the reaction also requires vitamin B6
136
Dopa decarboxylase requires what cofactor? What inhibits this cofactor?
Vitamin B6; carbidopa
137
What cofactor does dopamine -hydroxylase require?
Vitamin C
138
What cofactor does phenylethanolamine N-methyltransferase require?
S-adenosylmethionine
139
Dopamine is broken down to homovanillic acid via what two enzymes?
Monoamine oxidase and catechol-O-methyltransferase
140
Monoamine oxidase and catechol-O-methyltransferase break down norepinephrine to what product?
Vanillymandelic acid
141
Epinephrine is broken down to what product via monoamine oxidase and catechol-O-methyltransferase?
Metanephrine
142
In a normal individual, is tyrosine an essential or a nonessential amino acid?
Nonessential
143
True or False? Phenylketonuria is a disorder of branched-chain amino acid metabolism.
False; phenylketonuria is a disorder of aromatic amino acid metabolism (remember: **aromatic** amino acid metabolism = musty body **odor**)
144
What is an example of dietary phenylalanine?
Aspartame (eg, NutraSweet)
145
A woman with phenylketonuria learns she is pregnant; what would you advise her about her diet?
It is important to be strict about phenylalanine consumption, since it is a teratogen in women with phenylketonuria
146
Phenylketonuria can result from two defects:
(1) decreased levels of the enzyme _____ \_\_\_\_\_
or
(2) decreased levels of _____ \_\_\_\_\_.
Phenylalanine hydroxylase; tetrahydrobiopterin cofactor
147
In individuals with phenylketonuria, is tyrosine an essential or a nonessential amino acid?
Essential
148
An infant is found to have mental retardation and growth retardation. He has fair skin, eczema, and a musty body odor. What is this infant;s underlying metabolic disorder?
Phenylketonuria
149
What dietary modifications are used to treat phenylketonuria?
Decreasing phenylalanine and increasing tyrosine in the diet
150
A child has increased phenylacetate, phenyllactate, and phenylpyruvate in her urine. What is the underlying metabolic disorder?
Phenylketonuria
151
What type of inheritance pattern does phenylketonuria demonstrate?
Autosomal recessive
152
Normally, tyrosine can be made from what amino acid precursor?
Phenylalanine; however, patients with phenylketonuria lack the enzymes to carry out the reaction
153
What would a urinalysis show in a patient who has a deficiency of phenylalanine hydroxylase?
Elevated phenylketones
154
What might you see in an infant born to a mother with phenylketonuria and exposed to high in utero levels of phenylalanine?
Microcephaly, mental retardation, growth retardation, congenital heart defects
155
True or False? Phenylketonuria is screened for at birth.
True; it has a prevalence of 1:10,000 and is part of newborn screening in most states
156
A deficiency of which enzyme results in the disease alkaptonuria?
Homogentisic acid oxidase
157
Alkaptonuria results from a defect in the degradation of which amino acid?
Tyrosine
158
A patient submits a urine sample for routine urinalysis. A technician notes that it turns black upon standing. What is the underlying metabolic disorder?
Alkaptonuria
159
What are the signs and symptoms of alkaptonuria?
Dark connective tissue, debilitating arthralgias, pigmented sclerae
160
What is the prognosis for patients with alkaptonuria?
Alkaptonuria is a benign disease, although patients may suffer from arthralgias
161
What is the inheritance pattern of alkaptonuria?
Autosomal recessive
162
Albinism may be caused by a defect in the ability to synthesize melanin as a result of a deficiency in the enzyme \_\_\_\_\_, or it may result from a defect in the transporters of the amino acid \_\_\_\_\_.
Tyrosinase; tyrosine
163
Albinism involves decreased amounts of what substance and thus a lack of pigmentation?
Melanin
164
Which cells are the embryologic precursors of melanocytes?
Neural crest cells; failure of these cells to migrate results in albinism
165
Patients with albinism are at an increased risk for what type of cancer?
Skin cancer
166
How many parents must be carriers of a mutation for a child to have albinism secondary to mutated tyrosinase?
Two; this is an autosomal-recessive condition
167
Why does albinism show variable inheritance if it is an autosomal recessive disorder?
It exhibits locus heterogeneity
168
A patient with homocystinuria due to cystathionine synthase deficiency should be treated with which dietary modifications?
A diet that is low in methionine and high in cystine, vitamin B12, and folate
169
A patient has homocystinuria that is caused by a decreased affinity of cystathionine synthase for pyridoxal phosphate. What is the treatment?
Large doses of vitamin B6
170
Which amino acid, usually nonessential, becomes essential in patients with homocystinuria?
Cysteine
171
A defect in cystathionine synthase leads to what disorder?
Homocystinuria
172
A decrease in the affinity of cystathionine synthase for pyridoxal phosphate leads to what disorder?
Homocystinuria
173
A defect in homocysteine methyltransferase leads to what disorder?
Homocystinuria
174
Homocystinuria may be caused by which three defects?
A defect in cystathionine synthase, a decrease in the affinity of cystathionine synthase for its cofactor (pyridoxal phosphate), or a defect in homocystene methyltransferase
175
What test would you order in a patient who has advanced early atherosclerotic disease, tall stature, kyphosis, and lens subluxation?
Urine studies, looking for elevated homocysteine
176
A patient has mental retardation, osteoporosis, tall stature, lens subluxation, and a history of stroke and myocardial infarction. What is the underlying metabolic disorder?
Homocystinuria
177
What two amino acids can be produced from homocysteine?
Methionine and cysteine
178
The production of cysteine from homocysteine requires which vitamin as a cofactor?
Vitamin B6
179
What enzyme is required for the conversion of homocysteine to methionine?
Homocysteine methyltransferase
180
What enzyme is required for the conversion of homocysteine to cystathionine?
Cystathionine synthase
181
What cofactor is required for the conversion of homocysteine to methionine?
Vitamin B12
182
Cystinuria is a defect in an amino acid transporter that is located in which part of the body?
The proximal convoluted tubule of the kidney
183
What is the prevalence of cystinuria?
4.902777778
184
Cystinuria is a defect in the transport of which four amino acids?
Cysteine, ornithine, lysine, and arginine
185
What is the major clinical sequela of cystinuria?
Increased risk of staghorn calculi
186
What medication is used to treat cystinuria?
Acetazolamide (carbonic anhydrase inhibitor)
187
What symptom is characteristic of cystinuria?
Cystine kidney stones (cystine staghorn calculi)
188
How does acetazolamide prevent cystine stone formation?
It alkalinizes the urine, increasing the solubility of cystine
189
What is the molecular structure of cystine?
Two cysteine molecules connected by a disulfide bond
190
What is the inheritance pattern of cystinuria?
Autosomal recessive
191
Maple syrup urine disease is caused by a defect in what enzyme?
-Ketoacid dehydrogenase
192
Maple syrup urine disease is the result of the blocked degradation of what type of amino acids?
Branched amino acids
193
Which three branched amino acids are elevated in the blood of a patient with maple syrup urine disease?
Isoleucine, leucine, and valine (remember: **I L**ove **V**ermont maple syrup from maple trees, with **branches**)
194
What is the prognosis for a neonate diagnosed with maple syrup urine disease?
Most children with the disease die in infancy
195
What is Hartnup disease?
A disorder in which a defective neutral amino acid transporter leads to tryptophan wasting in the urine and gastrointestinal tract
196
What are the clinical signs and symptoms of Hartnup disease?
Hartnup disease causes pellagra due to inability to synthesize niacin; the result is diarrhea, dermatitis, and dementia
197
How is Hartnup disease inherited?
Autosomal recessive
198
Glucagon and epinephrine activate the second messenger cAMP via what enzyme?
Adenylyl cyclase
199
What two factors in muscle, by activating phosphorylase kinase, ensure that glycogenolysis is coordinated with muscle activity?
Calcium and calmodulin
200
What enzyme activates glycogen phosphorylase kinase?
Protein kinase A
